Surface plasmon resonance sensor comprising metal coated nanostructures and a molecularly imprinted polymer layer

ABSTRACT

A colorimetric sensor for detecting an analyte of interest that includes a metal layer disposed upon a substrate, a plurality of nanostructures, and a corresponding plurality of metal deposits spaced apart from the metal layer. The metal layer defines a plurality of holes, each nanostructure includes a first portion disposed within a respective hole, and each metal deposit is disposed upon a second portion of a respective nanostructure. The sensor also includes a molecularly imprinted polymer layer that may cover the metal layer, the nanostructures, and/or the metal deposits. The molecularly imprinted polymer layer defines a cavity shaped to receive the analyte of interest, and the sensor is configured such that, when an analyte contacts the molecularly imprinted polymer layer and becomes disposed within the cavity, an optical property of at least a portion of the sensor changes thereby to cause a detectable color change in and/or from the sensor.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of, claims priority to and thebenefit of, and incorporates by reference herein in its entiretyInternational Patent Application No. PCT/US2017/065333, which was filedon Dec. 8, 2017 and which claims priority to and the benefit of U.S.Provisional Patent Application No. 62/431,585, which was filed on Dec.8, 2016, and U.S. Provisional Patent Application No. 62/489,668, whichwas filed on Apr. 25, 2017, the contents of which are also incorporatedby reference herein in their entireties.

TECHNICAL FIELD

In various embodiments, the present invention relates to a colorimetricsensor for use in detecting the presence of a target molecule (analyte)in a fluid sample and, more specifically, to sub-wavelengthnanostructured color pixel arrays and plasmonic colorimetric sensors foruse in detecting the presence of a target molecule in a fluid sample.

BACKGROUND OF THE INVENTION

The use of agents to incapacitate an individual has become moreprevalent. Examples of such agents include gamma-butyrolactone (GBL),gamma-hydroxybutyrate (GHB), ketamine, Rohypnol, and the like. Forexample, the agents may be secretly placed in a beverage, such as analcoholic beverage, of the intended consumer. Because these and similaragents are colorless, substantially odorless, and hard to detect,methods and devices are needed to detect the presence of such agentsprior to consumption.

Although there are various techniques for detecting the presence of achemical substance in a subject after the subject has consumed such anagent (e.g., by urinalysis using liquid chromatography-tandem massspectrometry), such techniques are reactive in nature and merely confirmwhat may already be suspected, rather than proactive to detect the agentbefore it has been consumed. Furthermore, such techniques requireexpensive equipment run by highly trained technicians. Proactive testingdevices may require exposing a portion of the liquid to be tested to achemical reagent composition, which may result in a color change thatindicates the presence of the agent in the liquid sample. Unfortunately,such tests are time consuming and may not be discrete.

Additional testing apparatuses are available. For example, a subject mayuse drug testing strips that are hidden in or incorporated into, forexample, a match, a match book, a cocktail napkin, a coaster, aplacemat, a menu, and so forth. Although such approaches may appear morediscreet, the subject may nevertheless be placed in an awkward positionby having to perform the test. Moreover, the subject may have to carryout tests periodically over the course of a social encounter.

U.S. Pat. No. 9,285,352 describes an apparatus for testing a liquidusing a straw, a stirrer, and/or a beverage container, where anindicator adapted to provide a visible reaction, e.g., a color change,upon exposure to an agent of interest, is adhered or otherwise bonded toa portion of the straw, stirrer, and/or beverage container. Inparticular, the indicator may cause the straw, stirrer, and/or beveragecontainer, or the liquid contacting the straw, stirrer, and/or beveragecontainer, to change color and/or fluoresce when an agent of interest isdetected at or above a certain concentration.

Despite the advances made to date, there still exists a need forimproved devices (e.g., colorimetric sensors) and methods for detectingchemical substances of interest in a liquid sample.

SUMMARY OF THE INVENTION

The invention is based, in part, upon the discovery of a newcolorimetric sensor that can detect an analyte of interest in a fluid orliquid sample and that, in some implementations, may be disposed upon orintegrated within a surface of a fluid receptacle (e.g., a glass or acup) or a straw.

In a first aspect, the present invention relates to a colorimetricsensor for detecting an analyte of interest in a fluid sample. In someembodiments, the sensor includes a metal layer disposed upon a substrateand defining a plurality of holes, a plurality of nanostructures (e.g.,nanoposts and/or nanospheres) each of which includes a first portiondisposed within a respective one of the holes, a corresponding pluralityof metal deposits (e.g., metal nanodisks and/or metal caps) spaced apartfrom the metal layer each of which is disposed upon a second portion ofa respective one of the nanostructures (e.g., on a top surface of any ofthe nanoposts and/or on a top surface of any of the nanospheres), and amolecularly imprinted polymer layer that covers at least one of themetal layer, the nanostructures, and the metal deposits. In somevariations, the molecularly imprinted polymer layer defines a cavityshaped to receive an analyte of interest. In some applications, thesensor is configured so that, when an analyte contacts the molecularlyimprinted polymer layer and becomes disposed within the cavity, anoptical property of at least a portion of the sensor changes thereby,causing a detectable color change in and/or from the sensor.

In some implementations, each nanostructure is made from a dielectricmaterial, a second molecularly imprinted polymer, a blend of thedielectric material and the second molecularly imprinted polymer, and/ora dielectric material coated with the second molecularly imprintedpolymer. The nanostructures may be configured to provide a periodicdistribution from about 10 nanometers to about 2 micrometers. In someapplications, a first subset of nanostructures is configured as a firstsub-pixel to produce a first color and a second subset of nanostructuresis configured as a second sub-pixel to produce a second, differentcolor. In some variations, the nanostructures of the first subsetinclude a dimension(s) that differs from the dimension(s) of thenanostructures of the second subset and/or the nanostructures of thefirst subset are arranged to have a periodicity different from theperiodicity of the nanostructures of the second subset.

In some embodiments, the metal deposits are spaced apart from the metallayer by a distance between about 1 nanometer and about 2 micrometers.In some implementations, the molecularly imprinted polymer layer isoptically transparent. In some applications, the sensor is disposed uponor integrated within a surface of a fluid receptacle or a straw.

In a second aspect, the present invention relates to a method fordetecting an analyte of interest in a fluid sample. In some embodiments,the method includes the process steps of (a) contacting a colorimetricsensor with the fluid sample and (b) detecting whether a color changeoccurs when the sensor is contacted with the fluid sample. A colorchange is indicative that the analyte of interest is present in thefluid sample. In some applications, the sensor includes a metal layerdisposed upon a substrate and defining a plurality of holes, a pluralityof nanostructures (e.g., nanoposts and/or nanospheres) each of whichincludes a first portion disposed within a respective one of the holes,a corresponding plurality of metal deposits (e.g., metal nanodisksand/or metal caps) spaced apart from the metal layer each of which isdisposed upon a second portion of a respective one of the nanostructures(e.g., on a top surface of one of the nanoposts and/or nanospheres), anda molecularly imprinted polymer layer that covers at least one of themetal layer, the nanostructures, and the metal deposits. The molecularlyimprinted polymer layer may define a cavity shaped to receive an analyteof interest. In some applications, the sensor is configured such that,when an analyte contacts the molecularly imprinted polymer layer andbecomes disposed within the cavity, an optical property of at least aportion of the sensor changes thereby, causing a detectable color changein and/or from the sensor. In some variations, the method furtherincludes confirming that the analyte is present in the fluid sample byusing a spectrometer to detect the Raman spectra of the analyte.

In some implementations, each nanostructure is made from a dielectricmaterial, a second molecularly imprinted polymer, a blend of thedielectric material and the second molecularly imprinted polymer, and/ora dielectric material coated with the second molecularly imprintedpolymer. The nanostructures may be configured to provide a periodicdistribution from about 10 nanometers to about 2 micrometers. In someapplications, a first subset of the nanostructures is configured as afirst sub-pixel to produce a first color and a second subset of thenanostructures is configured as a second sub-pixel to produce a secondcolor. In some variations, the nanostructures of the first subsetinclude a dimension(s) that differs from the dimension(s) of thenanostructures of the second subset and/or the nanostructures of thefirst subset are arranged to have a periodicity that differs from theperiodicity of the nanostructures of the second subset.

In some embodiments, the metal deposits are spaced apart from the metallayer by a distance between about 1 nanometer and about 2 micrometers.In some implementations, the molecularly imprinted polymer layer isoptically transparent.

In a third aspect, the present invention relates to a method ofmanufacturing a colorimetric sensor capable of detecting an analyte ofinterest in a fluid sample. In some embodiments, the method includes:forming a plurality of nanostructures on a substrate, applying metal(e.g., aluminum, copper, silver, gold, platinum, tungsten, orcombinations thereof) to at least a portion of each nanostructure and toat least a portion of the substrate (e.g., by a metal depositionprocess), and covering at least one of the nanostructures and theapplied metal with a first molecularly imprinted polymer layer thatdefines a cavity shaped to receive an analyte of interest. In someimplementations, the sensor is configured such that, when an analytecontacts the first molecularly imprinted polymer layer and becomesdisposed within the cavity, an optical property of at least a portion ofthe sensor changes thereby to cause a detectable color change in and/orfrom the sensor.

In some applications, forming the nanostructures (e.g., nanoposts)includes coating a surface of the substrate with at least one of adielectric material, a second molecularly imprinted polymer, or a blendof the dielectric material and the second molecularly imprinted polymer,and imprinting (e.g., using a mold) the nanostructures in the coating.In some variations, the coating has a thickness between about 1nanometer and about 2 micrometers. In some implementations, the mold iscoated with a release agent, such as a fluorocarbon release agent, afluorosilane release agent, a polybenzoxazine release agent, orcombinations thereof.

In another application, forming the nanostructures (e.g., nanospheres)includes one or more of self-assembling a layer of colloidal nanosphereson a surface of the substrate and/or shrinking the nanospheres. In somevariations, the nanospheres are shrunk by an oxygen plasma process.Typical shrunk nanospheres may have a diameter between about 1 nanometerand about 2 micrometers. In some implementations, each nanosphere ismade from a dielectric material, a second molecularly imprinted polymer,and/or a blend of the dielectric material and the second molecularlyimprinted polymer.

The nanostructures may include a periodic distribution from about 10nanometers to about 2 micrometers. In some embodiments, a first subsetof the nanostructures is configured as a first sub-pixel to produce afirst color and a second subset of the nanostructures is configured as asecond sub-pixel to produce a second color. In some variations, thenanostructures of the first subset are configured with a dimension(s)that differs from the dimension(s) of the nanostructures of the secondsubset. In certain variations, the nanostructures of the first subsetare configured with a periodicity that differs from the periodicity ofthe nanostructures of the second subset.

In some embodiments, the substrate includes or is made from glass,plastic, metal, rubber, wood, cellulose, wool, or combinations thereof.In some applications, the substrate is a fluid receptacle (e.g., a cupor a glass) or a straw. In some applications, the first molecularlyimprinted polymer layer is optically transparent.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, like reference characters generally refer to the sameparts throughout the different views. For the purposes of clarity, notevery component may be labeled in every drawing. Also, the drawings arenot necessarily to scale, emphasis instead generally being placed uponillustrating the principles of the invention. In the followingdescription, various embodiments of the present invention are describedwith reference to the following drawings, in which:

FIG. 1A schematically illustrates a top perspective view of a plasmoniccolorimetric sensor having a plurality of rod-like metal-insulator-metal(MIM) nanostructures arranged in an array of nanoposts/nanopillars, inaccordance with a first embodiment of the invention;

FIG. 1B schematically illustrates a plan view of the plasmoniccolorimetric sensor of FIG. 1A, in accordance with some embodiments ofthe invention;

FIG. 1C schematically illustrates a cross-sectional view of theplasmonic colorimetric sensor of FIG. 1A and includes a detail ofreceptor cavities disposed in a protective layer made of a molecularlyimprinted polymer (MIP) material encasing the nanoposts/nanopillars, inaccordance with some embodiments of the invention;

FIG. 2 schematically illustrates a cross-sectional view of a plasmoniccolorimetric sensor having a plurality of MIM nanostructures arranged inan array of nanospheres and includes a detail of receptor cavitiesdisposed in a protective layer made of a MIP material encasing thenanospheres, in accordance with a second embodiment of the invention;

FIG. 3A schematically illustrates a cross-sectional view of theplasmonic colorimetric sensor of FIG. 1A and includes a detail ofreceptor cavities in the protective layer made of a MIP materialencasing the nanoposts/nanopillars, in accordance with some embodimentsof the invention;

FIG. 3B schematically illustrates a cross-sectional view of theplasmonic colorimetric sensor of FIG. 3A in which the cavities arefilled with an analyte target molecule, in accordance with someembodiments of the invention;

FIG. 4A schematically illustrates a cross-sectional view of theplasmonic colorimetric sensor of FIG. 2 and includes a detail ofreceptor cavities in the protective layer made of a MIP materialencasing the nanospheres, in accordance with some embodiments of theinvention;

FIG. 4B schematically illustrates a cross-sectional view of theplasmonic colorimetric sensor of FIG. 4A in which the cavities arefilled with an analyte target molecule, in accordance with someembodiments of the invention;

FIG. 5A schematically illustrates a plan view of a pixel having twosub-pixels that each have a plurality of subwavelength plasmonic MIMnanostructures, in accordance with some embodiments of the invention;

FIG. 5B schematically illustrates a view of the individual pixel of FIG.5A emitting a first color, in accordance with some embodiments of theinvention;

FIG. 5C schematically illustrates a view of an array of the pixels ofFIG. 5B, in accordance with some embodiments of the invention;

FIG. 6A schematically illustrates a cross-sectional view of the pixel ofFIG. 5A having plasmonic MIM nanostructures arranged in a firstsub-pixel and a second sub-pixel, in accordance with some embodiments ofthe invention;

FIG. 6B schematically illustrates a cross-sectional view of anotherillustrative pixel of a plasmonic colorimetric sensor for use in tandemwith the plasmonic colorimetric sensor of FIG. 6A, in accordance withsome embodiments of the invention;

FIG. 7A schematically illustrates a cross-sectional view of theplasmonic colorimetric sensor of FIG. 6A and includes a detail ofreceptor cavities in a protective layer made of a MIP material encasingthe nanostructures, in accordance with some embodiments of theinvention;

FIG. 7B schematically illustrates a cross-sectional view of theplasmonic colorimetric sensor of FIG. 7A in which the cavities arefilled with an analyte target molecule, in accordance with someembodiments of the invention;

FIG. 8 schematically illustrates a dual or side-by-side sensor having afirst sensor array and a second sensor array that each exhibit a changeof emitted light color after the binding of an analyte target moleculeto a cavity in the MIP material, in accordance with some embodiments ofthe invention;

FIGS. 9A through 9F schematically illustrate a top-down method ofmanufacturing the plasmonic colorimetric sensor of FIGS. 1A through 1C,in accordance with some embodiments of the invention;

FIGS. 10A through 10C schematically illustrate certain steps of atop-down method of manufacturing the plasmonic colorimetric sensor ofFIG. 6A, in accordance with some embodiments of the invention;

FIGS. 11A through 11E schematically illustrate a top-down method ofmanufacturing the plasmonic colorimetric sensor of FIG. 2, in accordancewith some embodiments of the invention; and

FIG. 12 schematically illustrates exemplary structures for use incombination with colorimetric sensors for detecting an analyte targetmolecule of interest in a fluid sample, in accordance with someembodiments of the invention.

DETAILED DESCRIPTION

To provide an overall understanding of the invention, certainillustrative embodiments will now be described, including devices (e.g.,colorimetric sensors), methods of making the devices, and methods ofdetecting an analyte target molecule of interest in a fluid sample.However, the devices and methods described herein may be adapted andmodified as appropriate for the application being addressed and thedevices and methods described herein may be employed in other suitableapplications. All such adaptations and modifications are to beconsidered within the scope of the invention.

Throughout the description, where compositions and devices such as asensor are described as having, including, or comprising specificcomponents, or where processes and methods are described as having,including, or comprising specific steps, it is contemplated that,additionally, there are compositions and devices of the presentdisclosure that consist essentially of, or consist of, the recitedcomponents, and that there are processes and methods according to thepresent disclosure that consist essentially of, or consist of, therecited processing steps.

In the application, where an element or component is said to be includedin and/or selected from a list of recited elements or components, itshould be understood that the element or component can be any one of therecited elements or components, or the element or component can beselected from a group consisting of two or more of the recited elementsor components.

Further, it should be understood that elements and/or features of adevice or a method described herein can be combined in a variety of wayswithout departing from the spirit and scope of the present disclosure,whether explicit or implicit herein. For example, where reference ismade to a particular feature, that feature can be used in variousembodiments of the devices of the present disclosure and/or in methodsof the present disclosure, unless otherwise understood from the context.In other words, within this application, embodiments have been describedand depicted in a way that enables a clear and concise application to bewritten and drawn, but it is intended and will be appreciated thatembodiments can be variously combined or separated without parting fromthe present teachings and disclosure(s). For example, it will beappreciated that all features described and depicted herein can beapplicable to all aspects of the disclosure(s) described and depictedherein.

The articles “a” and “an” are used in this disclosure to refer to one ormore than one (i.e., to at least one) of the grammatical object of thearticle, unless the context is inappropriate. By way of example, “anelement” means one element or more than one element.

The term “and/or” is used in this disclosure to mean either “and” or“or” unless indicated otherwise.

It should be understood that the expression “at least one of” includesindividually each of the recited objects after the expression and thevarious combinations of two or more of the recited objects unlessotherwise understood from the context and use. The expression “and/or”in connection with three or more recited objects should be understood tohave the same meaning unless otherwise understood from the context.

The use of the term “include,” “includes,” “including,” “have,” “has,”“having,” “contain,” “contains,” or “containing,” including grammaticalequivalents thereof, should be understood generally as open-ended andnon-limiting, for example, not excluding additional unrecited elementsor steps, unless otherwise specifically stated or understood from thecontext.

Where the use of the term “about” is before a quantitative value, thepresent disclosure also includes the specific quantitative value itself,unless specifically stated otherwise. As used herein, the term “about”refers to a ±10% variation from the nominal value unless otherwiseindicated or inferred.

Where a percentage is provided with respect to an amount of a componentor material in a composition such as a polymer, the percentage should beunderstood to be a percentage based on weight, unless otherwise statedor understood from the context.

Where a molecular weight is provided and not an absolute value, forexample, of a polymer, then the molecular weight should be understood tobe an average molecule weight, unless otherwise stated or understoodfrom the context.

It should be understood that the order of steps or order for performingcertain actions is immaterial so long as the present disclosure remainsoperable. Moreover, two or more steps or actions can be conductedsimultaneously.

At various places in the present specification, features are disclosedin groups or in ranges. It is specifically intended that the descriptioninclude each and every individual subcombination of the members of suchgroups and ranges. For example, an integer in the range of 0 to 40 isspecifically intended to individually disclose 0, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, and 40, and aninteger in the range of 1 to 20 is specifically intended to individuallydisclose 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, and 20.

The use of any and all examples, or exemplary language herein, forexample, “such as” or “including,” is intended merely to illustratebetter the present disclosure and does not pose a limitation on thescope of the disclosure unless claimed. No language in the specificationshould be construed as indicating any non-claimed element as essentialto the practice of the present disclosure.

Various aspects of the disclosure are set forth herein under headingsand/or in sections for clarity; however, it is understood that allaspects, embodiments, or features of the disclosure described in oneparticular section are not to be limited to that particular section butrather can apply to any aspect, embodiment, or feature of the presentdisclosure.

Surface Plasmon Resonance and Plasmonic Colorimetric Sensors

Surface plasmon resonance (SPR) is a phenomenon that generally occurswhen incident light strikes a metallic surface, where electromagneticfields, e.g., an electromagnetic surface wave, are very strong.Advantageously, spectral properties of the resonance, e.g., a plasmonicscattering profile resulting from reflected light waves having discretewavelengths, may be used to characterize the local environment,especially after the metallic nanoparticle surface and, moreparticularly, electrons located on the surface of the nanoparticle,i.e., the surface plasmons, have been excited by the incident light. Forexample, incident light, striking near or between metallic nanoparticlesurfaces and having a specific wavelength, excites surface plasmons,causing them collectively to oscillate. This oscillation generates asignificantly enhanced electromagnetic field. The added presence ofanalyte target molecules that adhere to or are associated with themetallic nanoparticle surfaces modify the local dielectric environment,further inducing a plasmonic scattering profile change that,advantageously, may lead to enhanced macroscopic color change that canbe used to detect and/or confirm the presence of an analyte targetmolecule in a fluid sample.

In the structure and design of plasmonic colorimetric sensors, thescattered or reflected color is primarily determined by a localizedplasmon resonance between two metal surfaces separated by a couplingdistance. According to the Mie theory, the size and shape of the metalsurfaces, e.g., nanoposts, nanopillars, nanospheres, and the like, alsoaffects the plasmon resonance. Likewise, periodicity between adjacentmetal surfaces also affects the plasmon resonance. For example, thecloser the metallic surfaces are to each other, the greater the couplingbetween the interacting dipoles of the two metallic surfaces. Thegreater the interactive dipole coupling, the greater the increase of theplasmon resonant wavelength. In contrast, the more distant the metallicsurfaces are from one another, the weaker the coupling between theinteracting dipoles, resulting in a decrease of the plasmon resonantwavelength.

In some embodiments, the plasmonic colorimetric sensors described hereininclude nanostructure antennas having an array of nanoposts,nanopillars, nanospheres, or the like. For such sensors, thenanoposts/nanopillars/nanospheres may be used to provide the couplingdistance between the two metallic surfaces. A first embodiment of aplasmonic colorimetric sensor having an array of metal-capped nanoposts,nanopillars, or the like is shown in FIGS. 1A through 1C, while a secondembodiment of a plasmonic colorimetric sensor having an array ofmetal-capped nanospheres is shown in FIG. 2.

The embodied sensor array 100 depicted in FIGS. 1A through 1C includes aplurality of rod-like, metal-insulator-metal (MIM) antenna structures 15that are formed, deposited, or the like on a base substrate 20. Theexemplary sensor array 200 depicted in FIG. 2 includes a plurality ofnanospheroidal MIM antenna structures 105 that are formed, deposited, orthe like on a base substrate 110. Aside from the characteristics, i.e.,the size, shape, dimensions, number, periodicity, etc., of the MIMantenna structures 15, 105 in the two embodiments, the exemplary sensors100, 200 work in substantially the same manner. More particularly, theMIM antenna structures 15, 105 may be configured to produce, in thepresence of an analyte target molecule and when struck by incident lightof a particular wavelength, an observable change in color within thevisible spectrum. Indeed, as mentioned herein, when incident light of aparticular wavelength strikes the MIM antenna structure 15, 105, thelight scattered by the sensors 100, 200 will produce an observable colorchange, providing presumptive evidence of the presence of the analytetarget molecule.

For the purpose of illustration and not limitation, the rod-like MIMantenna structures 15 in the sensor array 100 in FIGS. 1A through 1C maybe disposed on a base substrate 20 in, for example, a grid, for example,a 5×6 grid, with each antenna structure 15 having the same orsubstantially the same size, e.g., dimensions (height and width), andshape (cylindrical or substantially cylindrical), as well asperiodicity, i.e., spacing between adjacent antenna structures 15. Thoseof ordinary skill in the art can appreciate that the number andarrangement of the antenna structures 15 in the sensor array 100, aswell as the shape, size, and the like of each antenna structure 15 andthe periodicity between adjacent antenna structures 15 may be subject tothe design and purpose of the array 100.

In some variations, each MIM antenna structure 15 includes a nanopost ornanopillar 25 structured and arranged to have a desired shape, height,width, diameter, or other dimension, as well as periodicity, i.e.,spacing between adjacent nanoposts or nanopillars 25. In variousembodiments, the nanoposts or nanopillars may be manufactured from amolecularly imprinted polymer (MIP) material, from a dielectric orinsulative material (e.g., glass, SiO₂, polymer, and so forth), from adielectric material coated with a MIP material, and/or from a materialcomprising a blend of a MIP material and a dielectric material.Preferably, the MIP materials define cavities for attracting andcapturing and/or for adsorbing discrete analyte target molecules.Although FIG. 1A through 1C depict cylindrically-shaped orsubstantially-cylindrically-shaped nanopillars 25, that is done for thepurpose of illustration and not limitation. Indeed, in addition to beingcircular or round, exemplary nanopillar cross-sections may beelliptical, rectangular, square, triangular, polygonal, amorphous, andthe like. Typical heights for nanopillars may range between about one(1) nm and about 2000 nm, or between about 5 nm and about 1000 nm, orbetween about 10 nm and about 500 nm. Typical diameters for(cylindrical) nanopillars may range between about 10 nm and about 1000nm, or between about 15 nm and about 750 nm, or between about 20 nm andabout 500 nm. Typical spacing between adjacent nanopillars may rangebetween about 10 nm and about 2000 nm, or between about 15 nm and about1000 nm, or between about 20 nm and about 500 nm.

In some applications, the MIP material may generally be manufactured bypolymerization, e.g., by thermal and/or photochemical initiation, of amixture of monomers, cross-linkers, initiators, and/or porogens, orcombinations thereof and the like. Typical monomers include, for thepurpose of illustration and not limitation, carboxylic acids (e.g.,acrylic acid, methacrylic acid, vinylbenzoic acid, and trifluoromethylacrylic acid (TFMAA)), sulphonic acids (e.g.,2-acrylamido-2-methylpropane sulphonic acid), heteroaromatic bases(e.g., vinylpyridine and vinylimidazole), acrylamide,2-hydroxyethylmethacrylate (HEMA), and the like. Typical cross-linkersinclude, for the purpose of illustration and not limitation, ethyleneglycol dimethacrylate (EGDMA), trimethylolpropane trimethacrylate(TRIM), divinylbenzene (DVB), pentaerythritol triacrylate (PETRA), andthe like. Typical initiators include, for the purpose of illustrationand not limitation, acetyl peroxide, lauroyl peroxide, decanoylperoxide, caprylyl peroxide, benzoyl peroxide, tertiary butylperoxypivalate, sodium percarbonate, tertiary butyl peroctoate,azobis-isobutyronitrile (AIBN), and the like. Typical porogens include,for the purpose of illustration and not limitation, methanol,acetonitrile, toluene, mineral oil, and combinations thereof.

A portion or portions of the MIM antenna structure may include metallicmaterials, e.g., platinum, gold, silver, aluminum, copper, tungsten, andcombinations thereof. For example, as shown in FIG. 1A, each MIM antennastructure 15 in the sensor array 100 may include a thin (e.g., 0.1 nm toseveral hundreds of nanometers) metallic cap or nanodisk 30, e.g., thathas been formed or deposited on a first (e.g., top) surface of eachnanopillar 25. Furthermore, a thin (e.g., 0.1 nm to several hundreds ofnanometers) metallic back reflector layer, or backplane 35, may also bedeposited on the base substrate 20 about a second (e.g., bottom) surfaceof each nanopillar 25. In some embodiments, the base substrate is madeof, for example, glass, plastic, metal, wood, rubber, wool, cellulose,combinations thereof, and the like. In some variations, the metallicbackplane 35 includes a plurality of openings 40 (e.g., holes) throughwhich a portion of each nanopillar 25 of each MIM antenna structure 15extends or protrudes. Preferably, the size and shape of the openingscorrespond to the size and shape of the nanopillars. In some variations,the coupling distance between the upper surface of the metallicbackplane and the bottoms of the nanodisks is about one (1) nm to about2000 nm, or about 5 nm to about 1000 nm, or about 10 nm to about 500 nm.

The metallic backplane and nanodisks formed or disposed atop,respectively, each of the base substrate and the nanopillars providevertical limits for collecting and focusing incident light. With onlythe nanodisks present, for example, the optical scattering intensitywould be very low, making it difficult to observe the scattered color.By combining the nanodisks with the metallic backplane, however,plasmonic coupling between the upper and lower components may increaseor enhance the scattering intensity and the hues. Advantageously,plasmonic coupling between the nanodisks and the backplane may result ina vibrant color without viewing angle dependence. Indeed, the emittedstructural color due to the plasmonic coupling may differ from astructural color generated from, for example, dielectric photoniccrystals with which the emitted color may depend on the viewing angledue to the light diffraction principle.

For protection and to provide a cavity with which to capture an analyte,one, two, or all of the antenna structures 15, the metallic nanodisks30, and the metallic backplane 35 may be encased within anoptically-transparent protective layer 50. In some embodiments, theprotective layer 50 is manufactured of a molecularly imprinted polymer(MIP) material or of a blend of a dielectric material and a MIPmaterial. Here again, the MIP material may generally be made bypolymerization, e.g., by thermal and/or photochemical initiation, of amixture of monomers, cross-linkers, initiators, and/or porogens, orcombinations thereof and the like. The MIP material used for theprotective layer, or blended with a dielectric material for theprotective layer, may be the same or different from the MIP materialused in construction of the nanopillars. Preferably, the protectivelayer 50 defines cavities 55 produced by, for example, removing templatemolecules from the MIP materials. In some variations, the cavities areshaped to receive discrete analyte target molecules.

The cavities can be formed in a MIP by removing the analyte templatesfrom the MIP. The MIPs formed in this way may include a soluble andprocessible MIP synthesized following the three steps depicted below.Note that this is just an example as MIPS can be created using otherforms of polymerization.

Step 1. The preparation of a multi-armed RAFT reagent.

Step 2. The preparation of a crosslinkable and imprintable core withmulti-armed RAFT reagent, spacer monomer, and crosslinking monomer.

Step 3. Addition of template (ketamine as an example) for imprinting andcrosslinking process to make the MIP.

The resulting soluble and processible MIP can be blended with otherdielectric materials so that it can be applied to the sensor as both afunctional and a protective layer. Also, the MIPs can be made fromconventional polymerization methods to yield fine MIP powder orcolloidal nanoparticles that can be blended with other dielectricmaterials (such as UV-curable polymers).

The MIP protective layer can include a chemical moiety (e.g., a“receptor” or “binding site”) that can form a complex (e.g., host-guestchemistry) with an analyte target molecule of interest via anon-covalent bond, for example, via hydrogen bonding, metalcoordination, hydrophobic forces, van der Waals forces, π-πinteractions, halogen bonding, and/or electrostatic and/orelectromagnetic effects. Examples of such receptors include, but are notlimited to, urea, thiourea, guanidine, aminopyridine, or amidine,cucurbituril, cyclodextrin, calixarene, crown ether, porphyrin,phthalocyanine, and the like. See, e.g., Jonathan W. Steed, Jerry L.Atwood, Philip A. Gale, “Definition and Emergence of SupramolecularChemistry,” chapter in Supramolecular Chemistry: From Molecules toNanomaterials (2012). The use of such a receptor can facilitatepositioning of the analyte. For example, as shown in FIGS. 3A and 3B,such a receptor further can facilitate an analyte target molecule 60positioning itself within a cavity 55 formed or disposed on or withinthe protective layer 50 of MIP material.

The binding of analyte target molecules can result in an observablecolor change, e.g., from blue to red, within the visible light spectrum.Advantageously, the initial color before analyte binding may be tunedand optimized by varying the size and shape of the nanopillars, as wellas by varying the periodicity of the nanopillars on the sensor array.Although FIGS. 3A and 3B only show cavities 55 associated with andwithin the protective layer 50, if the nanopillars 25 are manufacturedof a MIP material, of a blended dielectric-MIP material, and/or of adielectric material coated with a MIP material, an analyte targetmolecule 60 may also position itself within a cavity formed or disposedon or within the nanopillars 25.

The protective layer and/or nanopillars, each of which can be a MIP, maybe formed by any molecular imprinting technique (e.g., a reversibleaddition-fragmentation chain transfer (RAFT) polymerization method, anatom-transfer radical polymerization (ATRP) method, a covalent bondingmethod, a self-assembly method, a hierarchical imprinting method, apolymerization packed bed method, or the like) that can leave a cavityin the protective layer or nanopillars, which cavity has an affinity toa chosen “analyte” molecule. In some techniques, the process may involveinitiating the polymerization of monomers in the presence of an analyteof interest that is extracted afterwards, thus leaving behind a cavitythat is complementary to the analyte. MIPs are described in greaterdetail in U.S. Pat. Nos. 8,241,575 and 9,285,352, the contents of whichare incorporated by reference herein in their entirety for all purposes.

For example, a MIP can be made from a monomer and a crosslinker. In someembodiments, a MIP can be made from a polymerizable monomer, optionallyhaving a receptor that can bind with an analyte molecule, such as a ureaor a thiourea receptor, and/or a cross-linkable monomer that containstwo or more reactive groups such as one vinyl moiety and one allylicmoiety. Each of the two or more reactive groups should have differentreactivities such that they can be employed in different stages of themanufacture of a MIP. For example, a vinyl group can be employed forincorporation into a pre-polymer for a MIP and a less reactive allylicgroup can be used as a crosslinker during the molecularly imprintingprocess. Other asymmetrically divinyl or vinyl/allyl or other monomerswith two double bonds of different reactivity can be used, for example,methacrylate-based divinyl monomers such as hex-5-enyl methacrylate.See, e.g., “Controlled Divinyl Monomer Polymerization Mediated by LewisPairs: A Powerful Synthetic Strategy for Functional Polymers,” ACS MacroLett., 2014, 3, 896-899 and “Branched polystyrene with abundant pendantvinyl functional groups from asymmetric divinyl monomer”, Journal ofPolymer Science: Part A: Polymer Chemistry, 2008, 46, 6023-6034.

Scheme I shows an example of forming, via RAFT polymerization, a“pre-polymer” (i.e., a polymer useful in the molecularly imprintingprocess) using a cross-linkable monomer having two reactive groups ofdifferent reactivities and a polymerizable monomer containing apolymerizable moiety and a urea receptor.

The result of RAFT polymerization of these reactants is a “pre-polymer”that includes the RAFT agent at a terminal end. The pre-polymertypically is a soluble pre-polymer, which facilitates further creationof the protective layer and nanopillars.

Subsequently, as shown in Scheme II below, the pre-polymer can becombined with an analyte of interest (“analyte template”) to perform themolecularly imprinting process thereby to create the cavities for theanalyte. More specifically, the pre-polymer and analyte interact toassociate the analytes with the urea receptors, which pre-polymer thencan be crosslinked to form the cavities after the analyte is removedfrom the MIP (e.g., by Soxlet extraction and/or solvent washingprocesses). As can be seen in Scheme II, a MIP can include a RAFT agentat its terminal end. Advantageously, the functional groups and modifiedfunctional groups of the RAFT agent, for example, a thiol group afterreduction of the depicted RAFT agent, can be used to secure the MIP to asubstrate as a coating layer such as in the top-down methods ofmanufacture discussed herein.

When an analyte target molecule is adsorbed into or bound to a cavity ofthe protective layer and/or one of the nanopillars, one or severalchanges may occur to produce the observable color change, e.g., from thecolor blue to the color red. For example, changes in the effectiverefractive index (n) in the localized environment of the MIP material(e.g., due to the presence of the analyte target molecule) may affectthe dipole interaction between the metallic nanodisks and the backplane.This dipole interaction determines the scattered hybridized plasmonresonance, i.e., the color. Alternatively, or in addition, adsorption ofthe analyte to the cavities may cause the nanopillars to swell (e.g.,increase in height), which, in turn, may modify, i.e., increase, thecoupling distance between the metallic nanodisks and the backplane.Increasing the coupling distance between the two metallic surfacesdecreases the coupling between the interacting dipoles of the metallicnanodisks and the metallic backplane, thereby decreasing the plasmonresonant wavelength. In turn, the reduced plasmon resonant wavelengthleads to an observable color change in the colorimetric sensor.

In various embodiments, analytes are adsorbed into or bound to cavitiesof both the protective layer and the nanopillars. Some analytes may, forexample, diffuse through the protective layer and into the nanopillarsdue to the porous nature of the relatively thin protective layer. Thepresence of the analytes in the cavities of both the protective layerand the nanopillars will thus cause both the protective layer and thenanopillars to expand, thereby increasing the coupling distance betweenthe metallic nanodisks and the backplane.

FIG. 2 depicts a sensor array 200 that includes a plurality ofspheroidal MIM antenna structures 105. The spheroidal MIM antennastructures 105 may be formed or disposed in a grid or pattern on a basesubstrate 110. Those of ordinary skill in the art can appreciate thatthe number and arrangement of the antenna structures in the sensorarray, the shape, size, dimensions, diameter, and the like of eachantenna structure, and the periodicity between adjacent antennastructures may be subject to the design and purpose of the sensor array.

In some applications, each MIM antenna structure 105 includes amonolayer of nanospheres 115 manufactured from a molecularly imprintedpolymer (MIP) material, from a dielectric or insulative material (e.g.,glass, SiO₂, polymer, and so forth), from a dielectric material coatedwith a MIP material, and/or from a material comprising a blend of a MIPmaterial and a dielectric material. The spheroidal-shaped orsubstantially-spheroidal-shaped nanospheres 115 depicted in FIG. 2 maybe oblate, prolate, and/or spherical. Typical diameters of thenanospheres may range between about 1 nm and about 2000 nm, or betweenabout 5 nm and about 1000 nm, or between about 10 nm and about 500 nm.Typical spacing between adjacent nanospheres may range between about 10nm and about 2000 nm, or between about 15 nm and about 1000 nm, orbetween about 20 nm and about 500 nm.

Some portion or portions of each antenna nanostructure 105 in a sensorarray may be made from metallic materials, e.g., platinum, gold, silver,aluminum, copper, tungsten, and combinations thereof. For example, asshown in FIG. 2, each MIM antenna structure 105 in the sensor array 200may include a thin (e.g., 0.1 nm to several hundreds of nanometers)metallic cap 120 that has been formed or deposited on or at the crown ofa first (e.g., top) surface of each nanosphere 115. A thin (e.g., 0.1 nmto several hundreds of nanometers) metallic back reflector layer, orbackplane 125, may also be deposited on the base substrate 110 about asecond (e.g., bottom) surface of each nanosphere 115. In someembodiments, the base substrate is made of, for example, glass, plastic,metal, wood, rubber, wool, cellulose, combinations thereof, and thelike. In some variations, the metallic backplane 125 includes aplurality of openings 130 (e.g., holes) through which a portion of eachnanosphere 115 of each MIM antenna structure 105 extends or protrudes.Preferably, the size and shape of the openings correspond to the sizeand shape of some portion of the nanospheres. In some variations, thecoupling distance between the upper surface of the metallic backplaneand the bottoms of the metallic caps is about one (1) nm to about 2000nm, or about 5 nm to about 1000 nm, or about 10 nm to about 500 nm.

The metallic backplane formed or disposed on the base substrate and themetallic caps formed or disposed on or at the crown of the nanospheresprovide vertical limits for collecting and focusing incident light. Withonly the metallic caps present, for example, the optical scatteringintensity would be very low, making it difficult to observe thescattered color. By combining the metallic caps with the metallicbackplane, however, plasmonic coupling between the upper and lowercomponents may increase or enhance the scattering intensity and thehues. Advantageously, plasmonic coupling between the metallic caps andthe backplane may result in a vibrant color without viewing angledependence. Indeed, the emitted structural color due to the plasmoniccoupling may differ from a structural color generated from, for example,dielectric photonic crystals with which the emitted color may depend onthe viewing angle due to the light diffraction principle.

Again referring to FIG. 2, one, two, or all of the antenna structures105, the metallic caps 120, and the metallic backplane 125 may beencased within a protective layer 135, which can be opticallytransparent. In some embodiments, the protective layer is manufacturedof a MIP material or of a blend of a dielectric material and a MIPmaterial. The MIP material used for the protective layer, or blendedwith a dielectric material for the protective layer, may be the same ordifferent from the MIP material used in construction of the nanospheres.

In some embodiments, the MIP material of the protective layer and/ornanospheres is made from the polymerization, e.g., by thermal and/orphotochemical initiation, of a mixture of monomers, cross-linkers,initiators, and/or porogens, or combinations thereof and the like.Typical monomers, cross-linkers, initiators, and/or porogens for the MIPmaterials of the protective layer and nanospheres can be the same asthose enumerated herein for the nanoposts/nanopillars and protectivelayer described with reference to FIGS. 1A through 1C. Preferably, theprotective layer 135 defines cavities 140 produced by, e.g., removingtemplate molecules from the MIP materials. In some variations, thecavities are shaped to receive discrete analyte target molecules.

As described herein, the MIP protective layer can include a chemicalmoiety (e.g., a “receptor” or “binding site”) that can form a complex(e.g., host-guest chemistry) with an analyte target molecule of interestvia a non-covalent bond. The use of such a receptor can facilitatepositioning of the analyte. For example, as shown in FIGS. 4A and 4B,such a receptor further can facilitate an analyte target molecule 145positioning itself within a cavity 140 formed or disposed on or withinthe protective layer 135 of MIP material. The binding of analyte targetmolecules results in an observable color change, e.g., from blue to red,within the visible light spectrum. Advantageously, the initial colorbefore analyte binding may be tuned and optimized by varying the sizeand shape of the nanospheres 115, as well as by varying the periodicityof the nanospheres 115 on the sensor array 200. Although FIGS. 4A and 4Bonly show cavities 140 associated with and within the protective layer135, if the nanospheres are manufactured of a MIP material, of a blendeddielectric-MIP material, and/or of a dielectric material coated with aMIP material, an analyte target molecule may also position itself withina cavity formed or disposed on or within the nanospheres.

Similar to a sensor having nanopillars, when an analyte target moleculeis adsorbed into or captured by or bound to a cavity within theprotective layer and/or on the nanospheres, one or several changes mayoccur to produce the observable color change, e.g., from the color blueto the color red. For example, changes in the effective refractive index(n) in the localized environment of the MIP material (e.g., due to thepresence of an analyte target molecule) may affect the dipoleinteraction between the metallic caps and the backplane. This dipoleinteraction determines the scattered hybridized plasmon resonance, i.e.,the color. Alternatively, or in addition, adsorption of the analyte tothe cavities may cause the nanospheres to swell (e.g., increase inheight and/or diameter), which, in turn, may modify, i.e., increase, thecoupling distance between the metallic caps and the backplane.Increasing the coupling distance between the two metallic surfacesdecreases the coupling between the interacting dipoles of the metalliccaps and the metallic backplane, thereby decreasing the plasmon resonantwavelength. In turn, the reduced plasmon resonant wavelength leads to anobservable color change in the colorimetric sensor.

In various embodiments, analytes are adsorbed into or bound to cavitiesof both the protective layer and the nanospheres. Some analytes may, forexample, diffuse through the protective layer and into the nanospheresdue to the porous nature of the relatively thin protective layer. Thepresence of the analytes in the cavities of both the protective layerand the nanospheres will thus cause both the protective layer and thenanospheres to expand, thereby increasing the coupling distance betweenthe metallic caps and the backplane.

Those of ordinary skill in the art can appreciate that a MIP material asdescribed herein may include any number of cavities appropriate toachieve the intended purpose. The number of cavities may, in part, bedetermined by the dissociation constant of the material used for the MIPmaterial. As different materials will have different dissociationconstants, the number of cavities present in the protective layer, inthe nanoposts/nanopillars, and/or in the nanospheres may depend upon thetype of material employed as the MIP material. In general, however, theaverage density of the cavities may be very high (e.g., up to 10¹⁰,10¹⁵, or 10 ²⁰ cavities per gram of MIP material). There may also besome variation in the number, density, and arrangement (e.g.,distribution or pattern) of the cavities in the MIP material.

Each formed cavity in a MIP should have an affinity for a correspondinganalyte target molecule of interest, which may include, for the purposeof illustration and not limitation, GBL, GHB, ketamine, Rohypnol, otherpharmaceutical grade drugs, bacteria, allergens and proteins,3-methyl-2-butene-1-thiol, substances that may be created during aprocess of creating 3-methyl-2-butene-1-thiol, substances that may becreated when beer is exposed to sunlight, congeners (e.g., producedduring fermentation and/or distillation of a beverage), and so forth.

Illustrative embodiments of nanostructure sensor arrays have beendepicted and described for instances in which the nanoposts/nanopillarsor nanospheres formed or disposed in a sensor array on a single basesubstrate share the same or substantially the same size, shape,periodicity, and so forth. Those of ordinary skill in the art canappreciate, however, that, in some applications of the presentinvention, one or more groupings of nanostructures may be formed ordisposed on a base substrate, such that one or more of the properties orparameters of one of the nanostructure groupings intentionally differsfrom the properties or parameters of another of the nanostructuregroupings, so as to produce different changes in the colors emitted bythe various nanostructure groupings. Indeed, at a microscopic (e.g.,pixel and sub-pixel) level, a first nanostructure grouping, having afirst set of design and structural properties, may be formed or disposedon a first portion of a base substrate, so as to emit, under a first setof operating conditions, a first color, while, under the same first setof operating conditions, a second nanostructure grouping, having asecond set of design and structural properties, may be formed ordisposed on a second portion of the base substrate, so as to emit asecond color that differs from the first color. Under a second set ofoperating conditions, the individual microscopic colors emitted by thefirst and second nanostructure groupings may produce a color changethat, at the macroscopic level of the array, becomes more pronounced ormore distinct.

For example, referring to FIGS. 5A through 5C, an exemplarysub-wavelength, nanostructured, color pixel array 300 for detecting thepresence of an analyte target molecule is shown. In some variations, thenanostructure sensor array 300 includes a plurality of pixels 350 that,for the purpose of illustration rather than limitation, are arranged inan 8×8 array. Those of ordinary skill in the art can appreciate that thenumber and the arrangement of the pixels 350 in the sensor array 300 maybe configured in accordance with design parameters to emit a macroscopiclevel color representative of the operating condition of the sensorarray 300 as a whole, i.e., as a combination of the microscopic coloremissions by the individual color pixels 350, as well as those of thenanostructure groupings, i.e., sub-pixels 310, 315 formed or disposed onthe base substrate 305 of each pixel 350.

For example, in some implementations, one or more pixels 350 in thenanostructure sensor array 300 may include a base substrate 305 on whicha first grouping of metal-insulator-metal (MIM) antenna structures 320,e.g., in a first sub-pixel 310, and on which a second grouping of MIMantenna structures 325, e.g., in a second sub-pixel 315, are formed ordisposed. In operation and by design, each sub-pixel 310, 315 may bestructured and arranged to emit, under a first set of operatingconditions, scattered light of a certain color that, in combination,produces light of a desired color associated with the pixel 350 (e.g.,Color X or red). For example, under the first set of operatingconditions, sub-pixel 310 may emit magenta-colored light and sub-pixel315 may emit yellow-colored light, which, when mixed together, producesred-colored light in the pixel 350. Under a second set of conditions,each sub-pixel 310, 315 may be structured and arranged to emit scatteredlight of a certain color that, in combination, provides a desired colorchange in the pixel 350. A combination of the colors of each of theplurality of pixels, under each of the first and the second sets ofconditions, in turn, produces a change or changes in the color or in apattern in the array sensor indicative of the respective condition.

In some applications, each pixel in the sensor array includes one ormore MIM antenna structures, i.e., plasmonic nanostructures, groupedinto any number of sub-pixels. For the purpose of this description, asub-pixel may be used to differentiate any grouping of MIM antennastructures having a first set of design properties or parameters, e.g.,size, shape, periodicity, and the like, from another grouping of MIMantenna structures having a second set of design properties orparameters, at least one of which differs from any of the first set ofdesign properties or parameters.

For the purpose of illustration and not limitation, the cross-sectionalview of FIG. 6A and the plan view of FIG. 5A show exemplary MIM antennastructures that are grouped into a first sub-pixel 310 of four MIMantenna structures 320 arrayed in a 2×2 grid and into a second sub-pixel315 also of four MIM antenna structures 325 arrayed in a 2×2 grid. Insome variations, each MIM antenna structure 320, 325 in each plasmonicsub-pixel 310, 315 may be a nanometer-sized, i.e., sub-wavelength,object typically including a nanopost or nanopillar 330, 335 separatingportions made from metallic materials, e.g., platinum, gold, silver,aluminum, copper, tungsten, and combinations thereof. These metallicmaterials, separated by the nanopillars 330, 335, provide and/or definevertical limits for collecting and focusing incident light.Advantageously, these MIM antenna structures 320, 325, and, morespecifically, the plasmonic sub-pixels 310, 315, may be configured toproduce, in the presence of an analyte target molecule and when struckby incident light of a particular wavelength, an observable color changeto provide presumptive evidence of the presence of the target analyte.

As shown in FIG. 6A, the exemplary pixel 350 for the sensor array 300may include the first sub-pixel 310 comprising or consisting essentiallyof a first plurality of MIM antenna structures 320 and the secondsub-pixel 315 comprising or consisting essentially of a second pluralityof MIM antenna structures 325. For illustrative purposes, thenanopillars 330 of the MIM antenna structures 320 associated with thefirst sub-pixel 310 may be wider (or thicker) and arranged with asmaller or shorter periodicity than the nanopillars 335 of the MIMantenna structures 325 associated with the second sub-pixel 315. Thediffering diameters and periodicity between the nanopillars 330 of theMIM antenna structures 320 associated with the first sub-pixels 310 andthe nanopillars 335 of the MIM antenna structures 325 associated withthe second sub-pixel 315 cause the respective subpixels 310, 315 toreflect or scatter light having a different wavelength and, hence,color.

In some variations, the nanopillars of the MIM antenna structuresassociated with the first and second sub-pixels may be made from a MIPmaterial, from a dielectric or insulative material (e.g., glass, SiO₂,polymer, and so forth), from a dielectric material coated with a MIPmaterial, and/or from a material comprising a blend of a MIP materialand a dielectric material. In some variations, the MIP materials used inthe nanopillars define cavities for attracting and adsorbing discreteanalyte target molecules. Although FIG. 5A and FIG. 6A depictrectangular or substantially-rectangular nanopillars, that is done forthe purpose of illustration and not limitation. Indeed, in addition tobeing rectangular, exemplary nanopillar cross-sections may beelliptical, circular, round, triangular, polygonal, amorphous, and thelike. Typical heights for nanopillars may range between about one (1) nmand about 2000 nm, or between about 5 nm and about 1000 nm, or betweenabout 10 nm and about 500 nm. Typical widths for nanopillars may rangebetween about 10 nm and about 1000 nm, or between about 15 nm and about750 nm, or between about 20 nm and about 500 nm. Typical spacing betweenadjacent nanopillars may range between about 10 nm and about 2000 nm, orbetween about 15 nm and about 1000 nm, or between about 20 nm and about500 nm.

In some applications, the MIP material may be manufactured bypolymerization as described herein. Typical monomers, cross-linkers,initiators, and/or porogens for the MIP materials of the nanopillars canbe the same as those enumerated herein for the nanoposts/nanopillars andprotective layer described with reference to FIGS. 1A through 1C.

A portion or portions of the MIM antenna structures may include metallicmaterials, e.g., platinum, gold, silver, aluminum, copper, tungsten, andcombinations thereof. For example, as shown in FIG. 6A, each MIM antennastructure 320, 325 in the pixel 350 may include a thin (e.g., 0.1 nm toseveral hundreds of nanometers) metallic cap or nanodisk 340 that hasbeen formed or deposited on a first (e.g., top) surface of eachnanopillar 330, 335. Furthermore, a thin (e.g., 0.1 nm to severalhundreds of nanometers) metallic back reflector layer, or backplane 345,may also be deposited on the base substrate 305 about a second (e.g.,bottom) surface of each nanopillar 330, 335. In some embodiments, thebase substrate is made of, for example, glass, plastic, metal, wood,rubber, wool, cellulose, combinations thereof, and the like. In somevariations, the coupling distance between the upper surface of themetallic backplane and the bottoms of the nanodisks is about one (1) nmto about 2000 nm, or about 5 nm to about 1000 nm, or about 10 nm toabout 500 nm.

The metallic backplane and nanodisks formed or disposed atop,respectively, each of the base substrate and the nanopillars providevertical limits for collecting and focusing incident light. With onlythe nanodisks present, for example, the optical scattering intensitywould be very low, making it difficult to observe the scattered color.By combining the nanodisks with the metallic backplane, however,plasmonic coupling between the upper and lower components may increaseor enhance the scattering intensity and the hues. Advantageously,plasmonic coupling between the nanodisks and the backplane may result ina vibrant color without viewing angle dependence. Indeed, the emittedstructural color due to the plasmonic coupling may differ from astructural color generated from, for example, dielectric photoniccrystals with which the emitted color may depend on the viewing angledue to the light diffraction principle.

For protection and to provide a cavity with which to capture an analyte,one, two, or all of the antenna structures 320, 325, the nanodisks 340,and the backplane 345 may be encased within a protective layer 360,which can be optically transparent. In some embodiments, the protectivelayer is manufactured of a MIP material or of a blend of a dielectricmaterial and a MIP material, where the MIP material is as describedherein. The MIP material used for the protective layer, or blended witha dielectric material for the protective layer, may be the same ordifferent from the MIP material used in construction of the nanopillars.Preferably, as previously described, the protective layer definescavities produced by, e.g., removing template molecules from the MIPmaterials. In some variations, the cavities are shaped to receivediscrete analyte target molecules.

The MIP protective layer can include a chemical moiety (e.g., a“receptor” or “binding site”) that can form a complex (e.g., host-guestchemistry) with an analyte target molecule of interest via anon-covalent bond, as described herein. For example, as shown in FIGS.7A and 7B, such a receptor further can facilitate an analyte targetmolecule 370 positioning itself within a cavity 365 formed or disposedon or within the protective layer 360 of MIP material. The binding ofanalyte target molecules 370 results in an observable color change,e.g., from blue to red, within the visible light spectrum. The initialcolor before analyte binding may be tuned and optimized by varying thesize and shape of the nanopillars, as well as by varying the periodicityof the nanopillars within each sub-pixel and between sub-pixels on thepixel.

When an analyte target molecule 370 is adsorbed into or bound to acavity 365 of the protective layer 360 and/or of the nanopillars 330,335, one or several changes may occur to produce the observable colorchange, e.g., from the color blue to the color red, as described herein.

In some implementations, the first sub-pixel may be configured toscatter, in the presence of incident light of a particular wavelength, afirst color, while the second sub-pixel may be configured to scatter, inthe presence of incident light of the same particular wavelength, asecond color that differs from the first color, collectively giving thepixel, in the absence of an analyte target molecule, a distinctive baseor background color. Advantageously, in the presence of an analytetarget molecule, e.g., that is adsorbed into or bound to a cavity of theprotective layer, the first and second sub-pixels each scatter adifferent color from before, which mix differently and cause the pixeland the sensor to emit an observable second color that differs from thebase color. It is this color change in the pixel, from the base color tothe second color, that is indicative of the presence of the analytetarget molecule, e.g., within a fluid sample.

In operation, at a microscopic (e.g., nanometer) level, each sub-pixelof the pixel may be adapted to emit a desired, e.g., constituent, color.For example, under certain circumstances, the first sub-pixel may bestructured and arranged to emit a first constituent color, e.g., magenta(M), while the second sub-pixel may be structured and arranged to emit adifferent, second constituent color, e.g., yellow (Y). Those of ordinaryskill in the art can appreciate that the pixel may include additionalsub-pixels emitting additional constituent colors, e.g., cyan (C) andthe like. Moreover, blank sub-pixels may be added to provide a black (K)color.

In a first mode of operation, i.e., before analyte target molecules arecaptured and/or bound in cavities formed in the MIP material of theprotective layer and/or of the nanopillars of the sub-pixels, theconstituent colors of magenta (M) and yellow (Y) of each sub-pixel mix,such that the pixel emits the color red (R). If the pixel includesadditional sub-pixels, e.g., sub-pixels capable of emitting cyan (C) orproviding a black (K) color, the blending of the constituent colors maybe controlled to emit any desired color. Advantageously, the ratio ofthe constituent colors M:Y can be controlled to be 1:1, or any desiredratio. When there are additional sub-pixels, the ratio, e.g., C:M:Y:K,can be controlled to provide any desired color.

At the macroscopic level (FIG. 5C), the sensor array 300, which may bemeasured in centimeters, may appear to the human eye as having a uniformcolor, e.g., red. This macroscopic, apparently uniform color resultsfrom the combination of the various colors emitted by each pixel 350 inthe array 300. Each pixel 350, which may be measured in microns, emitsthe appropriate color for the desired combination and ratio of itssub-pixels 310, 315, which may be measured in nanometers.

In a second mode of operation, i.e., once a fluid containing an analyteof interest is introduced to the sensor array and, more particularly, tothe protective layer or to either or both of the sub-pixels whosenanopillars include a MIP material, the presence of and binding of ananalyte target molecule in any of the cavities formed in MIP materialmay cause a color transformation. Indeed, in this second mode ofoperation, introduction and capture (or binding) of an analyte targetmolecule within one or more cavities in the MIP of the protective layerand/or of the nanopillars, modifies the local environment of the MIPmaterial, producing a color shift/change at the microscopic level of anyaffected sub-pixel and its corresponding pixel. For example, thecapture/binding of analyte target molecules within the cavities maymanifest as a sub-pixel color change, for example, from constituentcolor M to M′ or from constituent color Y to Y′. These microscopic colorchanges in affected sub-pixels mix to produce a consequent color changein corresponding pixel(s), which leads to a macroscopic color change inat least some portion of the sensor array.

In some applications, dual or multiple sensor arrays may be used intandem to provide confirmation of results and/or a greater degree ofaccuracy and assurance. For example, as shown in FIG. 8, a first sensorarray 300 having multiple first pixels 350 (see FIG. 6A) associatedtherewith and a second sensor array 300′ having multiple second pixels390 (see FIG. 6B) associated therewith may be disposed, e.g., in atandem or side-by-side arrangement, to provide evidence of the presenceof an analyte target molecule. In a first mode of operation, e.g.,before any target analyte is adsorbed by, captured in, or bound to acavity in the MIP material(s) in either of the sensor arrays, each ofthe arrays may emit a color X, e.g., blue, indicating that no targetanalyte is present. In a second mode of operation, e.g., after a targetanalyte is adsorbed by, captured in, or bound to a cavity in the MIPmaterial(s) in the sensor arrays, the first array may emit a first colorY, e.g., green, indicating that a target analyte is present, while thesecond array may emit a second color Z, e.g., yellow, indicating thatthe same target analyte is present. The contrast between the first colorY and the second color Z provides further visual confirmation that theanalyte target molecule is present. Those of ordinary skill in the artcan appreciate that in the design of the sub-pixels and pixels of eachsensor array, the size, shape, and periodicity of the MIM antennastructures can be structured and arranged to produce the first color Yand the second color Z, respectively, when the analyte target moleculeis present.

In addition, in various embodiments, the MIPs described herein candefine multiple cavities for multiple, different analytes, such that asingle one of the sensors described herein can detect the presence ofmultiple, different analytes. Alternatively, in certain embodiments, asensor described herein may be configured to detect the presence of onlya single analyte, but multiple ones of such sensors may be used intandem such that, together, the sensors can detect the presence ofmultiple, different analytes.

Additional Testing

Detection of a color change using any of the sensors or sensor arraysdescribed herein provides a presumption of the presence of the analytetarget molecule of interest. Further verification is possible bysubjecting the sample to additional testing that does not lend itself touse in the field. For example, surface-enhanced Raman scattering (SERS)is a spectroscopic method used in chemical and/or biological sensing forthe purpose of detecting individual molecules, e.g., analyte targetmolecules. More specifically, Raman scattering, using a spectrometercapable of detecting a molecular vibrational spectrum, is predicated onthe notion that any molecule of each analyte target will have a uniqueRaman scattering spectrum, displaying, upon illumination, e.g., by alaser light-emitting device, discrete, specific (Raman) peaks that canbe collected and used to identify or confirm the presence of the analytetarget molecule with a high degree of accuracy.

Methods of Manufacture

The colorimetric sensors described herein may be manufactured in avariety of manners. Exemplary top-down methods of manufacture aredescribed below.

Top-Down Methods of Manufacture

Referring to FIGS. 9A through 9F, an exemplary top-down method toproduce the sensor of FIGS. 1A through 1C is shown. In a first step(FIGS. 9A and 9B), a thin layer of a material 90 may be applied to,coated on, or formed on the surface of a substrate 92. In someimplementations, the thin layer of material 90 may be made of, forexample, a molecularly imprinted polymer (MIP) material, a dielectric orinsulative material (e.g., glass, SiO₂, polymer, and so forth), and/or amaterial comprising a blend of one or more MIP materials and adielectric material. The substrate may be made of, for example, glass,plastic, metal, wood, rubber, wool, cellulose, combinations thereof, andthe like. In some embodiments, the thin layer of material is spin-coatedonto the substrate. The thin layer of material 90 may be thick enough toresult (following the imprinting step described below) innanoposts/nanopillars 25 having a height that falls within a rangebetween about 1 nm and about 2000 nm, or between about 5 nm and about1000 nm, or between about 10 nm and about 500 nm. For example, thestarting thickness of the thin layer of material may be slightly greaterthan the desired finishing height of the resultingnanoposts/nanopillars.

In a next step (FIGS. 9C and 9D), the thin layer of material 90 may beimprinted by a mold 94, e.g., made of silicone or some other suitablemold material such as silicon (Si), polyethylene terephthalate (PET), aUV-curable resin, and the like. In some implementations, the mold 94 mayinclude solid portions 96 and openings 98 that are structured andarranged to provide a negative or mirrored image of the desired array ofnanoposts, nanopillars, or the like. The design of the solid portion 96and openings 98 may be configured to provide the resulting array 100 ornanoposts, nanopillars 25, or the like with a desired periodicity.Although the shapes and sizes of the solid portions 96 and of theopenings 98 in the mold 94 shown in FIG. 9C are the same orsubstantially the same, those of ordinary skill in the art canappreciate that the solid portions 96 and openings 98 of the mold 94 maybe manufactured to provide nanoposts, nanopillars, or the like of anydesired shape with any desired dimensions and at any desiredperiodicity. Typical heights of the resulting nanoposts/nanopillars mayrange between about one (1) nm and about 2000 nm, or between about 5 nmand about 1000 nm, or between about 10 nm and about 500 nm. Theperiodicity of the post array may range between about 10 nm and about2000 nm, or between about 15 nm and about 1000 nm, or between about 20nm and about 500 nm. The diameter of cylindrical nanopost/nanopillarsmay range between about 10 nm and about 1000 nm, or between about 15 nmand about 750 nm, or between about 20 nm and about 500 nm.

In some variations, prior to imprinting the layer, a very thin layer orcoating of a releasing agent, e.g., fluorocarbon, fluorosilane,polybenzoxazine, combinations thereof, and the like, may be applied tothe surfaces of the solid portions of the mold, to facilitate removal ofthe mold from the resulting array of nanoposts/nanopillars. The verythin layer or coating of the releasing agent can be a self-assembledmonolayer (SAM) or multiple layers with a thickness from less than aboutone (1) Angstrom to about 10 nm.

Following the imprinting of the nanoposts/nanopillars, they may be curedvia photo—(e.g., using ultraviolet (UV) light) or thermal-initiatedpolymerization. In the case where the nanoposts/nanopillars aredielectric materials to be coated with a MIP material, a thin (e.g., 0.1nm to 100 nm thick) adhesion layer of silica may be applied (e.g., viachemical vapor deposition (CVD), physical vapor deposition (PVD),electron beam evaporation, or sputtering) to the exterior surfaces ofthe nanoposts/nanopillars 25 shown in FIG. 9D. Then, a soluble andprocessible MIP may be applied (e.g., via spin-coating or dip-coating)to the silica surface as a thin (e.g., 0.1 nm to 100 nm thick) coatingprior to the metal deposition depicted in FIG. 9E.

In a next step (FIG. 9E), a thin layer (e.g., of about 0.1 nm to severalhundred nanometers) of metal, e.g., platinum, gold, silver, aluminium,copper, tungsten, combinations thereof, and the like, may be deposited,e.g., by metal deposition, chemical vapor deposition (CVD), sputtering,three-dimensional nanoprinting, plasma-enhanced chemical vapordeposition (PECVD), physical vapor deposition (PVD), electrolessplating, and so forth, on the surface of the substrate 92 and on a topsurface of the nanoposts/nanopillars 25 in the array. Deposition on thesurface of the substrate 92 may form a continuous metal film 35 withopenings (e.g., holes), while deposition on the top surfaces of thenanoposts/nanopillars 25 forms metal nanodisks 30.

In a next step (FIG. 9F), the nanoposts/nanopillars 25, nanodisks 30,and continuous metal film 35 may be coated with an optically transparentprotective layer 50 to protect the sensor array from abrasion andscratching. In some variations, the protective layer may be made of oneor more MIP materials or, alternatively, one or more MIP materialsblended with one or more dielectric materials. The blend may range fromabout 1% MIP materials/99% dielectric materials to about 99% MIPmaterials/1% dielectric materials. Advantageously, as previouslyexplained, the protective layer may include a plurality of cavities andserve as the analyte target molecule capturing agent for the sensorarray. Accordingly, in some embodiments, a greater percentage of MIPmaterials is preferable in the blend, as it provides for a greaternumber of cavities to capture the analytes of interest. For example, theblend may include 60% MIP materials, 70% MIP materials, 80% MIPmaterials, 90% MIP materials, 95% MIP materials, or more. In someembodiments, the protective layer is applied by spin-coating and isphoto- or thermally-initiated for polymerization.

FIGS. 10A through 10C illustrate the use of an exemplary mold 94′ in atop-down manufacturing method to produce the sensor of FIG. 6A. Thesteps for producing the nanoposts/nanopillars 330, 335 for each of thesub-pixels 310, 315 in the sensor array 300 may be essentially the sameas those previously described in connection with FIGS. 9A through 9F.The molds 94, 94′, however, differ. More particularly, in someapplications, the mold 94′ for producing the nanoposts/nanopillars 330,335 for each of the sub-pixels 310, 315 in the sensor array 300 mayinclude solid portions 96 a-96 e and openings 98 a and 98 b havingnon-uniform dimensions, so as to produce a first sub-pixel 310 withwider (i.e., thicker), more closely-spaced nanoposts/nanopillars 330 anda second sub-pixel 315 with thinner, less densely-spacednanoposts/nanopillars 335.

Referring to FIGS. 11A through 11E, an exemplary top-down method toproduce the nanosphere sensor array 200 of FIG. 2 is shown. In a firststep (FIGS. 11A and 11B), colloidal nanospheres 115 made of, forexample, a molecularly imprinted polymer (MIP) material, a dielectric orinsulative material (e.g., glass, SiO₂, polymer, and so forth), and/or amaterial comprising a blend of one or more MIP materials and adielectric material, may be formed or self-assembled, e.g., as a closelypacked monolayer, on the surface of a substrate 110. As before, thesubstrate may be made of, for example, glass, plastic, metal, wood,rubber, wool, cellulose, combinations thereof, and the like. Thediameters of the nanospheres may range between about 10 nm and about3000 nm, or between about 20 nm and about 2000 nm, or between about 30nm and about 1000 nm. In some embodiments, the nanospheres are formed asa monolayer on the substrate via dip-coating or spin-coating ofcolloidal nanospheres.

In a next step (FIG. 11C), the nanospheres 115 may be shrunk, e.g., byan oxygen plasma process or the like, until the diameters of theshrunken nanospheres 115′ are between about 1 nm and about 2000 nm, orbetween about 5 nm and about 1000 nm, or between about 10 nm and about500 nm. For example, the closely-packed nanosphere array may be subjectto oxygen plasma etching so that the diameter of the nanospheres becomessmaller due to the etching process.

In a next step (FIG. 11D), a thin layer (e.g., of about 0.1 nm toseveral hundred nanometers) of metal, e.g., platinum, gold, silver,aluminium, copper, tungsten, combinations thereof, and the like, may bedeposited, e.g., by metal deposition, chemical vapor deposition (CVD),sputtering, three-dimensional nanoprinting, plasma-enhanced chemicalvapor deposition (PECVD), physical vapor deposition (PVD), electrolessplating, and so forth, on the surface of the substrate 110 and on or atthe crowns of the nanospheres 115′. Deposition on the surface of thesubstrate 110 may form a continuous metal film 125 with openings (e.g.,holes) about the nanospheres 115′, while deposition on the top surfacesof the nanospheres 115′ forms metal caps 120.

In a next step (FIG. 11E), the continuous metal film 125, metal caps120, and arranged nanospheres 115′ may be coated with an opticallytransparent protective layer 135 to protect the sensor array fromabrasion and scratching. In some variations, the protective layer may bemade of one or more MIP materials. Alternatively, the protective layermay be made of one or more MIP materials blended with one or moredielectric materials. The blend may range from about 1% MIPmaterials/99% dielectric materials to about 99% MIP materials/1%dielectric materials. Advantageously, as previously explained, the MIPprotective layer may also define a plurality of cavities for capturinganalyte target molecules of interest. Accordingly, in some embodiments,a greater percentage of MIP materials is preferable in the blend, as itprovides for a greater number of cavities to capture the analytes ofinterest. For example, the blend may include 60% MIP materials, 70% MIPmaterials, 80% MIP materials, 90% MIP materials, 95% MIP materials, ormore. In one embodiment, the protective layer 135 is applied byspin-coating and is photo or thermally initiated for polymerization.

Practice of the invention will be more fully understood from thefollowing example, which is presented herein for illustrative purposesonly, and should not be construed as limiting the invention in any way.

Example

In various embodiments, for example referring to FIG. 12, any of thesensors or sensor arrays described herein may be operatively disposedupon or integrated within a surface of a substrate 700. In its normal orcustomary use, the substrate 700, the surface thereof, and the sensor orsensor array disposed upon or integrated within that surface are exposedto a liquid 705 in which an analyte target molecule of interest may ormay not be present. For the purpose of illustration and not limitation,exemplary substrates 700 include a straw 710, a swizzle stick or stirrer715, a fluid receptacle 720 (e.g., a cup, a glass, and the like), and soforth.

In a first step, a fluid sample to be interrogated, e.g., a beverage, isbrought into contact with the sensor or sensor array. This may occur,for example, by pouring the beverage into a fluid receptacle into whichthe sensor or sensor array has been integrated; by inserting a straw,stirrer, or swizzle stick into which the sensor or sensor array has beenintegrated into the beverage; and so forth. In some applications, visualindicia of the sensor or sensor array after initial contact with thebeverage may provide a neutral or “safe” reading, e.g., the sensor orsensor array may emit blue light. If an analyte of interest isintroduced into the beverage, a color change in the sensor or sensorarray, e.g., from blue to red, indicates that analyte is present in thefluid sample. Thus, in a second step, the sensor or sensor arrayproduces a color change when it comes into contact with the beverage.Advantageously, the sensor or sensor array may be able to detect thepresence of an analyte of interest for an extended period of time, suchthat a single sensor or sensor array may be used to continue to detectfor hours whether or not an analyte of interest is present in thebeverage.

INCORPORATION BY REFERENCE

The entire disclosures of each of the patent documents and scientificarticles cited herein are incorporated by reference herein in theirentirety for all purposes.

EQUIVALENTS

The invention may be embodied in other specific forms without departingfrom the spirit or essential characteristics thereof. The foregoingembodiments are therefore to be considered in all respects illustrativerather than limiting on the invention described herein. Scope of theinvention is thus indicated by the appended claims rather than by theforegoing description, and all changes that come within the meaning andrange of equivalency of the claims are intended to be embraced therein.

What is claimed is:
 1. A colorimetric sensor for detecting an analyte ofinterest in a fluid sample, the sensor comprising: a metal layerdisposed upon a substrate and defining a plurality of holes; a pluralityof nanostructures, each nanostructure comprising a first portiondisposed within one of the holes; a corresponding plurality of metaldeposits spaced apart from the metal layer, each metal deposit disposedupon a second portion of one of the nanostructures; and a molecularlyimprinted polymer layer covering at least one of the metal layer, theplurality of nanostructures and the plurality of metal deposits, themolecularly imprinted polymer layer defining a cavity shaped to receivean analyte of interest, wherein the sensor is configured such that, whenan analyte contacts the molecularly imprinted polymer layer and becomesdisposed within the cavity, an optical property of at least a portion ofthe sensor changes thereby to cause a detectable color change in thesensor.
 2. The sensor of claim 1, wherein the nanostructures arenanoposts.
 3. The sensor of claim 2, wherein the metal deposits aremetal nanodisks.
 4. The sensor of claim 3, wherein each metal nanodiskis disposed upon a top surface of one of the nanoposts.
 5. The sensor ofclaim 1, wherein the nanostructures are nanospheres.
 6. The sensor ofclaim 5, wherein the metal deposits are metal caps.
 7. The sensor ofclaim 6, wherein each metal cap is disposed upon a top surface of one ofthe nanospheres.
 8. The sensor of claim 1, wherein each nanostructurecomprises at least one of a dielectric material, a second molecularlyimprinted polymer, a blend of the dielectric material and the secondmolecularly imprinted polymer, or the dielectric material coated withthe second molecularly imprinted polymer.
 9. The sensor of claim 1,wherein the plurality of nanostructures comprise a periodic distributionfrom about 10 nanometers to about 2 micrometers.
 10. The sensor of claim1, wherein the plurality of nanostructures comprises a first subset ofnanostructures configured as a first sub-pixel to produce a first colorand a second subset of nanostructures configured as a second sub-pixelto produce a second color.
 11. The sensor of claim 10, wherein thenanostructures of the first subset comprise dimensions different fromthe nanostructures of the second subset.
 12. The sensor of claim 10,wherein the nanostructures of the first subset comprise a periodicitydifferent from the nanostructures of the second subset.
 13. The sensorof claim 1, wherein the plurality of metal deposits are spaced apartfrom the metal layer by a distance between about 1 nanometer and about 2micrometers.
 14. The sensor of claim 1, wherein the molecularlyimprinted polymer layer is optically transparent.
 15. The sensor ofclaim 1, wherein the sensor is disposed upon or integrated within asurface of a fluid receptacle or a straw.
 16. A method for detecting ananalyte of interest in a fluid sample, the method comprising: (a)contacting a colorimetric sensor with the fluid sample, the sensorcomprising: (i) a metal layer disposed upon a substrate and defining aplurality of holes; (ii) a plurality of nanostructures, eachnanostructure comprising a first portion disposed within one of theholes; (iii) a corresponding plurality of metal deposits spaced apartfrom the metal layer, each metal deposit disposed upon a second portionof one of the nanostructures; and (iv) a molecularly imprinted polymerlayer covering at least one of the metal layer, the plurality ofnanostructures and the plurality of metal deposits, the molecularlyimprinted polymer layer defining a cavity shaped to receive an analyteof interest, wherein the sensor is configured such that, when an analytecontacts the molecularly imprinted polymer layer and becomes disposedwithin the cavity, an optical property of at least a portion of thesensor changes thereby to cause a detectable color change in the sensor;and (b) detecting whether a color change occurs when the sensor iscontacted with the fluid sample, wherein a color change is indicativethat the analyte is present in the fluid sample.
 17. The method of claim16, wherein the nanostructures are nanoposts.
 18. The method of claim17, wherein the metal deposits are metal nanodisks.
 19. The method ofclaim 18, wherein each metal nanodisk is disposed upon a top surface ofone of the nanoposts.
 20. The method of claim 16, wherein thenanostructures are nanospheres.
 21. The method of claim 20, wherein themetal deposits are metal caps.
 22. The method of claim 21, wherein eachmetal cap is disposed upon a top surface of one of the nanospheres. 23.The method of claim 16, wherein each nanostructure comprises at leastone of a dielectric material, a second molecularly imprinted polymer, ablend of the dielectric material and the second molecularly imprintedpolymer, or the dielectric material coated with the second molecularlyimprinted polymer.
 24. The method of claim 16, wherein the plurality ofnanostructures comprise a periodic distribution from about 10 nanometersto about 2 micrometers.
 25. The method of claim 16, wherein theplurality of nanostructures comprises a first subset of nanostructuresconfigured as a first sub-pixel to produce a first color and a secondsubset of nanostructures configured as a second sub-pixel to produce asecond color.
 26. The method of claim 25, wherein the nanostructures ofthe first subset comprise dimensions different from the nanostructuresof the second subset.
 27. The method of claim 25, wherein thenanostructures of the first subset comprise a periodicity different fromthe nanostructures of the second subset.
 28. The method of claim 16,wherein the plurality of metal deposits are spaced apart from the metallayer by a distance between about 1 nanometer and about 2 micrometers.29. The method of claim 16, wherein the molecularly imprinted polymerlayer is optically transparent.
 30. The method of claim 16 furthercomprising confirming that the analyte is present in the fluid sample byusing a spectrometer to detect the Raman spectra of the analyte.
 31. Amethod of manufacturing a colorimetric sensor capable of detecting ananalyte of interest in a fluid sample, the method comprising: (a)forming a plurality of nanostructures on a substrate; (b) applying metalto at least a portion of each nanostructure and to at least a portion ofthe substrate; and (c) covering at least one of the plurality ofnanostructures and the applied metal with a first molecularly imprintedpolymer layer that defines a cavity shaped to receive an analyte ofinterest, wherein the sensor is configured such that, when an analytecontacts the first molecularly imprinted polymer layer and becomesdisposed within the cavity, an optical property of at least a portion ofthe sensor changes thereby to cause a detectable color change in thesensor.
 32. The method of claim 31, wherein step (a) comprises: (i)coating a surface of the substrate with at least one of a dielectricmaterial, a second molecularly imprinted polymer, or a blend of thedielectric material and the second molecularly imprinted polymer; and(ii) imprinting the plurality of nanostructures in the coating.
 33. Themethod of claim 32, wherein the coating comprises a thickness betweenabout 1 nanometer and about 2 micrometers.
 34. The method of claim 32,wherein the plurality of nanostructures are imprinted using a mold. 35.The method of claim 34, wherein the mold is coated with a release agent.36. The method of claim 35, wherein the release agent comprises at leastone of a fluorocarbon release agent, a fluorosilane release agent, apolybenzoxazine release agent, or combinations thereof.
 37. The methodof claim 31, wherein the nanostructures are nanoposts.
 38. The method ofclaim 31, wherein step (a) comprises self-assembling a layer ofcolloidal nanospheres on a surface of the substrate.
 39. The method ofclaim 38, wherein step (a) further comprises shrinking the nanospheres.40. The method of claim 39, wherein the nanospheres are shrunk by anoxygen plasma process.
 41. The method of claim 39, wherein each shrunknanosphere comprises a diameter between about 1 nanometer and about 2micrometers.
 42. The method of claim 38, wherein each nanospherecomprises at least one of a dielectric material, a second molecularlyimprinted polymer, or a blend of the dielectric material and the secondmolecularly imprinted polymer.
 43. The method of claim 31, wherein theplurality of nanostructures comprise a periodic distribution from about10 nanometers to about 2 micrometers.
 44. The method of claim 31,wherein the plurality of nanostructures comprises a first subset ofnanostructures configured as a first sub-pixel to produce a first colorand a second subset of nanostructures configured as a second sub-pixelto produce a second color.
 45. The method of claim 44, wherein thenanostructures of the first subset comprise dimensions different fromthe nanostructures of the second subset.
 46. The method of claim 44,wherein the nanostructures of the first subset comprise a periodicitydifferent from the nanostructures of the second subset.
 47. The methodof claim 31, wherein the substrate comprises at least one of glass,plastic, metal, rubber, wood, cellulose, wool, or combinations thereof.48. The method of claim 31, wherein the substrate is a fluid receptacleor a straw.
 49. The method of claim 48, wherein the fluid receptacle isa cup or a glass.
 50. The method of claim 31, wherein the metal isapplied by a metal deposition process.
 51. The method of claim 31,wherein the metal comprises at least one of aluminum, copper, silver,gold, platinum, tungsten, or combinations thereof.
 52. The method ofclaim 31, wherein the first molecularly imprinted polymer layer isoptically transparent.